自体造血干细胞移植治疗合并乙型肝炎病毒感染的弥漫大B细胞淋巴瘤患者的有效性和安全性分析

目的 探讨自体造血干细胞移植(auto-HSCT)治疗合并乙型肝炎病毒(HBV)感染的弥漫大B细胞淋巴瘤(DLBCL)患者的有效性、安全性和生存获益。方法 回顾性分析2008年8月至2020年8月于北京大学肿瘤医院接受auto-HSCT治疗的39例初治合并HBV感染的DLBCL患者资料,采用Kaplan-Meier生存曲线进行生存分析。结果 全组患者移植前后的完全缓解率分别为56.41%和71.79%,移植后3年无进展生存率及总生存率分别为38.46%和58.97%,39例患者均获得造血重建。结论 auto-HSCT用于治疗合并HBV感染的DLBCL是安全有效的,可明显改善患者预后。     

一线自体造血干细胞移植治疗老年人初治中高危或高危弥漫大B细胞淋巴瘤临床分析

目的探讨一线自体造血干细胞移植(auto-HSCT)巩固治疗老年人初治中高危/高危弥漫大B细胞淋巴瘤(DLBCL)的疗效及相关影响因素。方法回顾性分析2015年1月至2020年8月在宁波大学附属人民医院接受auto-HSCT的国际预后指数(IPI)≥3分的初治老年DLBCL患者的临床特征、治疗效果及预后因素。结果全部31例患者中男18例、女13例, 中位年龄65(60～75)岁;13例(41.9%)淋巴结外受累部位≥2处, 13例(41.9%)骨髓累及, IPI中高危(3分)21例(67.7%)、高危(≥4分)10例(32.2%);移植前疾病处于完全缓解(CR)21例(67.7%)、部分缓解(PR)10例(32.3%)。所有患者均获得造血重建, 中性粒细胞植入、血小板植入中位时间分别为10(9～16)d、12(8～58)d。移植后中位随访20.9(3.1～73.0)个月, 100 d内移植相关死亡率为3.2%(1/31), 2年总生存(OS)率、无进展生存(PFS)率分别为(77.2±8.4)%、(72.7±8.3)%。多因素Cox回归分析结果显示, 移植前部分缓解状态[OS(HR=3...     

3例复发难治性B细胞急性淋巴细胞白血病的治疗及移植物抗宿主病预防

目的 通过对3例复发难治性B细胞急性淋巴细胞白血病(B-ALL)患者的治疗方法及移植治疗后移植物抗宿主病(GVHD)的预防方法分析,总结这类疾病有效治疗方案及预防方案.方法 3例复发难治性B-ALL患者中2例为费城染色体Ph(+),在确定半相合供者后,给予CD19靶向嵌合抗原受体T(CAR-T)细胞桥接治疗,缓解后接受亲缘半相合异基因造血干细胞移植(haplo-HSCT),采用造血干细胞移植方案GIAC进行移植治疗,同时在移植后给予小剂量环磷酰胺(PTCY,14.5 mg/kg体质量)预防GVHD.结果 3例B-ALL患者CAR-T细胞治疗后均获得了完全缓解(CR),其中2例达分子生物学缓解,1例达流式MRD阴性缓解;其中2例患者顺利接受haplo-HSCT,回输后均成功供者细胞造血重建,无严重GVHD,白血病疾病状态稳定.另1例伴有p.T315I突变的Ph(+)-ALL患者,CAR-T细胞治疗后获得短暂分子生物学缓解,但在移植准备过程中再次复发后失去移植机会.结论 CAR-T治疗后序贯亲缘半相合移植治疗复发难治性B-ALL患者效果良好;小剂量PTCY联合GIAC移植方案可以安全有效地预防GVHD的发生;CAR-T细胞治疗后短期再次复发的B-ALL患者目前仍然治疗困难.     

造血干细胞移植治疗非霍奇金淋巴瘤研究进展

利妥昔单抗等新药问世后,非霍奇金淋巴瘤(NHL)的疗效显著提高,但对于高危及难治复发患者,造血干细胞移植(HSCT)仍是挽救患者生命的惟一手段。自体造血干细胞移植(ASCT)主要应用于一线治疗后复发的NHL,但在预后不良的淋巴瘤亚型,如套细胞淋巴瘤(MCL)及外周T细胞淋巴瘤(PTCL)可做为一线巩固治疗;对化疗敏感是最重要的预后因素。异基因造血干细胞移植(allo-HSCT)在NHL治疗中应用越来越多,尤其是减低剂量预处理(RIC)移植,因其较低的移植相关死亡率(TRM)及移植物抗淋巴瘤(GVL)效应而具有广阔的应用前景。但其适应证、移植的时机、预处理方案的选择等问题尚需多中心、随机的、前瞻性的临床试验进一步验证。     

马法兰200 mg/m2异基因清髓性方案治疗多发性骨髓瘤合并乙肝病毒感染

多发性骨髓瘤(Multiple Myeloma,MM)属于恶性浆细胞克隆增生性疾病,临床研究证明超大剂量放化疗配合造血干细胞移植可明显改善治疗结果。受多发性骨髓病患者年龄及疾病本身的影响,目前多采用非清髓性异基因造血干细胞移植治疗本病,但移植后植入失败及疾病复发为影响预后的不良因素。为达到最佳治疗效果,我们应用马法兰(Mel)200mg/m2清髓性方案治疗2例MM患者,获得成功,现将结果报告如下。1病例资料例1患者,男,38岁,确诊MM(IgG型)7个月,为行造血干细胞移植入院,移植前共给予5个疗程VAD方案(地塞米松40mg,d14,d912,d17-20;长春新碱0.5mg,…     

Bu+Vp16预处理方案行自体造血干细胞移植治疗急性髓系白血病27例临床疗效分析

正自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)较常规化疗能更好地清除瘤细胞,对于预后分层为低、中危的急性髓系白血病(acute myeloid leukemia,AML)患者,经过auto-HSCT治疗多可获得长期无病生存[1],且适用年龄范围广、所需经费较少、安全性高、移植后的并发症少、生活质量高。因此,auto-HSCT成为没有找到合适供者、经费困难患者     

同基因造血干细胞移植治疗白血病的临床疗效观察

目的探讨同基因造血干细胞移植(syn-HSCT)治疗白血病的临床效果。方法观察1996年1月至2008年8月中山大学附属第一医院血液科收治的7例syn-HSCT治疗白血病患者的造血重建情况、远期疗效及移植相关并发症,以108例异基因全相合造血干细胞移植(allo-HSCT)、50例自体造血干细胞移植(auto-HSCT)为对照。结果采用syn-HSCT、allo-HSCT和auto-HSCT治疗的3组患者中性粒细胞≥0.5×109/L的时间分别为(13.5±3.1)d、(14.6±4.5)d和(12.9±4.1)d,血小板≥20×109/L的时间分别为(18.7±7.3)d、(21.2±5.1)d和(25.3±9.4)d,3组之间比较差异无统计学意义(P>0.05);syn-HSCT组和allo-HSCT组比较,5年无病存活(DFS)率、总存活(OS)率及复发率比较差异均无统计学意义(P>0.05),但这两组与auto-HSCT组比较,在5年DFS、OS及复发率方面差异均有统计学意义(P<0.05);与allo-HSCT比较,syn-HSCT与auto-HSCT都具有较低的移植相关并发症和移植相关病死率。结论syn-HSCT具有存活率高、复发率低、移植相关并发症及病死率少的优点,可作为治疗白血病的有效方法。     

自体造血干细胞移植后DC-CIK细胞预防急性白血病复发的效果探讨

目的 探讨白血病自体造血干细胞移植后应用树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK细胞)预防急性白血病复发的临床疗效.方法 4例白血病自体造血干细胞移植后静注及腹股沟注射DC-CIK 细胞3次,观察疾病的复发情况以及DC-CIK细胞输注后的不良反应.结果 3例治疗后持续完全缓解(CR),CR期分别为32、36、45个月;1例急性非淋巴细胞白血病(M4)复发后进行异基因半相合造血干细胞移植,无病生存24个月.结论 DC-CIK细胞治疗可能协助清除微小残留病、预防复发,可作为白血病自体造血干细胞移植后预防复发的有效方法.     

自体造血干细胞移植治疗多发性硬化中的植入综合征

目的:总结自体造血干细胞移植(auto-HSCT)治疗多发硬化(MS)过程中植入综合征(ES)的发生情况.方法:应用auto-HSCT治疗继发性MS 24例,移植前EDSS评分为5.5(4～7.5).移植方法为应用G-CSF 5 μg/kg4～6 d动员,CS-3000细胞分离机采集外周血单个核细胞,对其中18例患者进行CD34 细胞分选.BEAM方案预处理.结果:移植后外周血中性粒细胞≥0.5×109/L的平均时间为11 d(9～13).共有6例患者在移植后 8～ 12 d出现非感染性发热,体温在38～40℃,持续1～5 d.其中2例伴皮肤充血性皮疹,持续4～5 d.短疗程应用皮质激素或仅对症治疗后上述症状均可缓解.结论:在auto-HSCT后中性粒细胞恢复期出现发热、皮疹时,应考虑ES的诊断,短疗程激素治疗对轻度ES有效,但应警惕出现呼吸衰竭或多器官衰竭的可能.     

FABC预处理异基因造血干细胞移植治疗难治未缓解急性白血病临床研究

目的观察FABC预处理异基因造血干细胞移植治疗未缓解急性白血病(AL)患者的疗效及安全性。方法收集2005年11月至2010年8月广东省人民医院采用FABC预处理方案进行异基因造血干细胞移植治疗18例难治未缓解AL患者。观察造血恢复、植入率、急慢性移植物抗宿主病发生率、移植相关病死率、复发、总存活率和无病存活率及预后因素分析。结果所有患者均于移植后14～21 d获得完全供者植入,中性粒细胞>0.5×109/L和血小板>20×109/L中位时间分别为12(7～72)d和13(7～60)d;急性移植物抗宿主病(GVHD)及慢性GVHD累积发生率分别为50%和73.3%。中位随访10.5(3.1～66.6)个月,移植相关病死率5.6%(1/18),复发率为36.8%(7/18)。1年的预期总生存(OS)率和无病生存(DFS)率分别是(58.9±13.2)%和(53.6±15.5%)。COX逐步回归模型分析显示,慢性GVHD是DFS独立有利因素。结论 FABC预处理异基因造血干细胞移植是治疗难治性未缓解AL安全有效的方法。     

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

Patients undergoing autologous hematopoietic stem cell transplantation (auto-HSCT) for autoimmune disease may have an added propensity to develop a second autoimmune disorder, given the genetic predisposition to autoimmunity. Therefore, we undertook a retrospective analysis of all patients who have undergone auto-HSCT for an autoimmune disease in our institution to determine the occurrence of a second autoimmune disorder and possible risk factors. In all, 155 patients underwent auto-HSCT for various autoimmune diseases; of those patients, 6 manifested a distinct secondary autoimmune disease at a median of 8.5 months (range, 2-30 months) after auto-HSCT. There were 2 patients with systemic lupus erythematosus, conditioned with a regimen containing antithymocyte globulin (ATG), who developed factor VIII inhibitors with severe bleeding. There were 4 patients (2 with multiple sclerosis, one each with lupus and systemic sclerosis) who received an alemtuzumab-containing conditioning regimen who developed autoimmune cytopenias. Among the 155 patients, the frequency of secondary autoimmune complications was 16.0% with alemtuzumab (4/25), 1.9% for ATG (2/102), and 0% for conditioning regimens without lympho-depleting antibodies (0/28)-a difference that was found to be significantly higher with alemtuzumab exposure (P = .011). In contrast, sex, type of ATG used, and CD34-selection of peripheral blood stem cells were not found to be significantly associated with development of a secondary autoimmune disorder.     

Autologous Peripheral Blood Stem Cell Transplantation for Severe Multiple Sclerosis

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.     

儿童难治性自身免疫性疾病自体外周血干细胞动员采集和分选的临床研究

目的 探讨儿童难治性自身免疫性疾病进行自体外周血干细胞动员采集的安全性和CD34+细胞分选纯化的可行性及其临床意义.方法 8例儿童难治性自身免疫性疾病,包括4例系统性红斑狼疮、2例皮肌炎,1例幼年型类风湿关节炎和1例多发性硬化,予行CD34+细胞纯化的自体外周血干细胞移植.首先采用环磷酰胺(CTX)联合粒细胞集落刺激因子(G-CSF)方案动员外周血干细胞,然后采用CS-3000血细胞分离机采集外周血,通过CliniMACS细胞分选仪分选自体外周血CD34+细胞,将其用保养液配置冻存于-80℃冰箱.采用非清髓内去除T的预处理方案,即卡氮芥+足叶乙苷+阿糖胞苷+马法兰+抗胸腺球蛋白(ATG)或CTX+ATG或CTX+马法兰+ATG,于第0天回输自体外周血CD34+细胞.结果 儿童能够耐受自体外周血干细胞动员采集过程,无动员相关死亡,动员后获得的单个核细胞数和CD34+细胞数的平均值分别为8.35×108/kg和7.92×106/kg,纯化后的白体外周血CD34+和CD3+细胞数的平均值分别为6.28×106/kg和0.71×105/kg.回输后中性粒细胞和血小板的植入中位时间分别为+11d和+15 d.结论 经CTX联合G-CSF方案可动员出足量的外周血干细胞,经CS-3000血细胞分离机采集可获得足够的单个核细胞,在动员过程中原发病无明显进展恶化,患儿能耐受动员方案,采集过程顺利安全;经CliniMACS细胞分选仪分选的自体外周血CD34+细胞纯度高,移植后造血恢复;采用CD34+细胞纯化的自体外周血移植治疗是常规治疗无效的儿童难治性自身免疫性疾病的可选择治疗措施之一.     

Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone

Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.     

Tandem autologous hematopoietic stem cell transplantation for treatment of adult T-cell lymphoblastic lymphoma: a multiple center prospective study in China

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and no standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) for adult T-LBL and evaluated prognostic factors affecting survival. A total of 181 newly-diagnosed adult T-LBL patients were enrolled: 89 patients were treated with chemotherapy alone, 46 were allocated to the single auto-HSCT group, 46 were treated with tandem auto-HSCT. Median follow-up time was 37 months; the 3-year progression/relapse rate of the tandem auto- HSCT group was significantly lower than that of the single auto-HSCT and chemotherapy groups (26.5% vs. 53.1% and 54.8%). The 3-year progression- free survival (PFS) and overall survival (OS) rates of the tandem auto- HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplant impacted OS and PFS. Multivariate analysis identified that disease status after the first transplant was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8⁺CD28⁺/CD8⁺CD28^– T-cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto- HSCT can be considered an optimal strategy for adult T-LBL patients. (Study registered at: ChiCTR-ONN-16008480).     

The influence of diagnostic bronchoscopy on clinical outcomes comparing adult autologous and allogeneic bone marrow transplant patients

STUDY OBJECTIVES: To review our experience with diagnostic bronchoscopy in the evaluation of pulmonary infiltrates in adult hematopoietic stem cell transplantation (HSCT) recipients in the era of Pneumocystis prophylaxis and cytomegalovirus antigen testing. The study focused on diagnostic yields and the influence of bronchoscopic findings on pharmacologic therapy and mortality, comparing allogeneic (allo) HSCT patients to autologous (auto) HSCT patients. DESIGN: Case series review. SETTING: Tertiary care academic urban medical centers. PATIENTS: All adult allo-HSCT and auto-HSCT patients undergoing bronchoscopy for the evaluation of pulmonary infiltrates from January 1997 to September 2001. MEASUREMENTS AND RESULTS: The review identified 169 bronchoscopies that had been performed on HSCT patients, representing 12.5% of all HSCT patients (allo-HSCT patients, 125 bronchoscopies; auto-HSCT patients, 44 bronchoscopies). Bronchoscopy was requested more often in allo-HSCT patients (18.7%) compared to auto-HSCT patients (6.6%). Findings at bronchoscopy provided a specific diagnosis more frequently in allo-HSCT patients (50%) compared to auto-HSCT patients (34%). For both allo-HSCT and auto-HSCT patients, most diagnoses were obtained by BAL alone, whereas transbronchial biopsy (TBBx) provided additional specific information in < 10% of cases. For select patients (n = 27), surgical lung biopsy following bronchoscopy provided unique diagnoses in 47 to 50% of cases. Information from bronchoscopy influenced clinical decisions more often in allo-HSCT patients (50%) than in auto-HSCT patients (36%), and allowed for the discontinuation or addition of antimicrobial, corticosteroid, or antineoplastic agents to treatment. Complications from bronchoscopy occurred in 9% of all HSCT patients (n = 15), and were associated with higher in-hospital mortality rates in allo-HSCT patients (82%; n = 9) compared to auto-HSCT patients (50%; n = 2). The overall in-hospital mortality rates for allo-HSCT and auto-HSCT patients having bronchoscopy was similar (38% vs 27%, respectively; p = 0.25), and establishing a specific diagnosis by bronchoscopy did not improve the in-hospital mortality rate for allo-HSCT or auto-HSCT patients. CONCLUSIONS: Bronchoscopy may provide clinically useful information in the evaluation of adult allo-HSCT and auto-HSCT recipients with pulmonary infiltrates. The results of testing BAL fluid samples alone suggested an etiology in most cases, whereas the findings of TBBx provided unique diagnoses infrequently. Further studies are warranted to improve the utility of diagnostic bronchoscopy in the evaluation of HSCT patients.     

Efficacy and safety of hematopoietic stem cell remobilization with plerixafor+G-CSF in adult patients with germ cell tumors

Autologous hematopoietic SCT (auto-HSCT) can be curative for patients with germ cell tumors. Poor stem cell mobilization jeopardizes the ability to deliver this therapy. Herein, we describe a retrospective study examining safety and efficacy of plerixafor in combination with G-CSF for patients with germ cell tumors who had previously failed stem cell collection. Overall, 21 patients with germ cell tumors and previous mobilization failure were remobilized with G-CSF (10?μg/kg SC) and plerixafor (0.24?mg/kg SC) beginning the evening of day 4 of G-CSF treatment. Dosing of G-CSF and plerixafor was repeated until collection of 2 × 10(6) CD34+ cells/kg. Remobilization resulted in a median yield of 3.2 × 10(6) CD34+ cells/kg. A total of 17 (81%) patients collected 2 × 10(6) and 9 (43%) patients collected 4 × 10(6) CD34+ cells/kg in a median of 2 (range 1-3) and 3 (range 1-4) days, respectively. In all, 16 (76%) patients proceeded to transplant; 8 (38%) received tandem transplants. There were no serious adverse events. In summary, the majority of patients with germ cell tumors who failed prior mobilization with growth factors ± chemotherapy were remobilized with plerixafor plus G-CSF facilitating at least one auto-HSCT. Use of plerixafor plus G-CSF can increase access of this potentially life-saving procedure to patients with high-risk germ cell tumors.     

High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis

High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes.     

High-dose melphalan with autologous hematopoietic stem cell transplantation for acute myeloid leukemia: results of a retrospective analysis of the Italian Pediatric Group for Bone Marrow Transplantation

This retrospective study from the Italian Association of Pediatric Hematology Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the results of consolidation with high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1). From October 1994 to July 1999, 20 patients (median age 9.9 years, range 0.11-16.2) were treated in six centers. Eighteen had de novo AML and two had secondary AML. According to BFM criteria, 10 were classified as standard- and 10 as high-risk patients, respectively. The median time from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months (range 0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging with either mafosfamide (three) or in vivo interleukin-2 (four) was performed in seven of 20 patients. Melphalan was administered at a dosage of 150-220 mg/m(2) (median 180). Median total number of nucleated cells infused was 2.5 x 10(8)/kg (range 1.1-8.9). The myeloablative regimen was well tolerated with no toxic death, veno-occlusive disease or life-threatening complications. All patients had hematopoietic recovery in a median time of 27 days for neutrophils and 44 days for platelets. Eight of 20 patients relapsed after a median time of 7.2 months from transplant (range 5.7-15.9). Six of them died (five of progression of disease and one of sepsis) while the remaining two patients are alive in CR2. The 3-year cumulative probability of survival and event-free-survival (EFS) is 62% and 56%, respectively. This study showed that in pediatric patients with AML consolidation of CR1 with high-dose melphalan allows survival and EFS to be obtained comparable to other auto-HSCT or chemotherapy published series with a potential sparing effect both on duration of treatment (with respect to chemotherapy) and on long-term side-effects (with respect to auto-HSCT with TBI or busulfan containing regimens).     

Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRObeta

SB-251353 is an N-terminal truncated form of the human CXC chemokine GRObeta. Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood stem cell mobilization and transplantation models. SB-251353 rapidly and transiently mobilized hematopoietic stem cells and neutrophils into the peripheral blood after a single subcutaneous injection. Transplantation of equivalent numbers of hematopoietic stem cells mobilized by SB-251353 into lethally irradiated mice resulted in faster neutrophil and platelet recovery than stem cells mobilized by granulocyte colony-stimulating factor (G-CSF). A single injection of SB-251353 in combination with 4 days of G-CSF administration resulted in augmented stem and progenitor cell mobilization 5-fold greater than G-CSF alone. Augmented stem cell mobilization could also be demonstrated in mice when a single injection of SB-251353 was administered with only one-day treatment with G-CSF. In addition, SB-251353, when used as a single agent or in combination with G-CSF, mobilized long-term repopulating stem cells capable of hematopoietic reconstitution of lethally irradiated mice. In rhesus monkeys, a single injection of SB-251353 induced rapid increases in peripheral blood hematopoietic progenitor cells at a 50-fold lower dose than in mice, which indicates a shift in potency. These studies provide evidence that the use of SB-251353 alone or in combination with G-CSF mobilizes hematopoietic stem cells with long-term repopulating ability. In addition, this treatment may (1) reduce the number of apheresis sessions and/or amount of G-CSF required to collect adequate numbers of hematopoietic stem cells for successful peripheral blood cell transplantation and (2) improve hematopoietic recovery after transplantation.